The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification.

The fine-tuned operation of the nervous system is accomplished by a diverse set of neurons which differ in their morphology, biochemistry and, consequently, their functional properties. The accurate interconnection between different neuron populations and their target tissues is the prerequisite for physiologically appropriate information processing. This is exemplified by the regulatory action of the autonomic nervous system in vertebrates to sustain homeostasis under changing physiological demands. For this purpose, the coordination of divergent regulatory responses is required in a multitude of tissues spread over the entire body. To meet this task, diverse neuronal populations interact at different levels. In the sympathetic system. chemical relations between preganglionic and postganglionic neurons appear to differ along the rostrocaudal axis. In addition, postganglionic neurons innervating different target tissues at a segmental level have distinct properties. Differences in their preganglionic innervation and their integrative membrane properties result in diverse activation patterns upon reflex stimulation. Moreover, postganglionic neurons differ in the transmitter molecules they employ to convey information to the target tissues. The segregation of noradrenaline and acetylcholine to different populations of postganglionic sympathetic neurons is well established. A combination of cellular and molecular approaches has begun to uncover how such a complex system may be generated during development. Growth and transcription factors involved in noradrenergic and cholinergic differentiation are characterised. Interestingly, they can also promote the expression of proteins involved in transmitter secretion. As the proteins participating in the vesicle cycle are expressed in many neuron populations, whereas the enzymes of transmitter biosynthesis are restricted to subpopulations of neurons, the findings suggest that early in neuronal development subpopulation-specific and more widely expressed neuronal properties can be commonly induced. Still, many details concerning the signals involved in the induction of the neurotransmitter synthesis and release machinery remain to be worked out. Likewise, the regulatory processes resulting in differences of electrophysiological membrane properties and the specific recognition between pre- and postganglionic neurons have to be determined. Ultimately, this will lead to an understanding at the molecular level of the development of a nervous system with diverse neuronal populations that are specifically interconnected to distinct input neurons and target tissues as required for the performance of a complex regulatory function.